Gene duplication followed by divergence of gene function is widely accepted as an important mechanism of adaptation in evolution. Multigene families in eukaryotes provide circumstantial evidence for this postulate. In addition, there is direct evidence for the selective advantage of duplications from experiments in microbial evolution. However, to date there is no direct evidence that divergence of function may occur subsequent to gene duplication. The specific aim of this proposal is to provide direct evidence for the divergence of the function of duplicated genes in an evolving population of the yeast Saccharomyces cerevisiae, and thus establish gene duplication and divergence as an important evolutionary strategy. We will analyse adaptive changes in different long-term populations of S. cerevisiae carrying three major categories of duplications of the structural gene for acid phosphatase. The populations will be grown in chemostats, with growth limited by the concentration of two organic phosphates. Two environmental designs will be used; one where the two organic phosphates are present simultaneously ("fine-grained environment") and one where growth is limited by alternating the phosphate source ("coarse-grained"). The long term objective of this study is to analyse the genetic and biochemical mechanisms of adaptation and evolution in a model organism in this case S. cerevisiae. As well as being important to population genetics and evolution, these studies will provide important information on the evolution of proliferating cell populations. The complete understanding of cell proliferation is critically important to many aspects of medicine, not the least of which is the treatment of cancer.